MCH is a hypothalamus-derived hormone known to have an appetite increasing action. Furthermore, it has been reported that MCH knockout mouse behaves normally but shows a significantly decreased food intake amount and a lighter body weight as compared to normal mouse (Nature, vol. 396, page 670, 1998). Furthermore, MCH receptor-1-deficient mice have been reported to show a lean phenotype (Proc. Natl. Acad. Sci. USA, vol. 99, page 3240, 2002). Therefrom MCH receptor (particularly MCH receptor 1) antagonists are expected to be excellent appetite suppressants or anti-obesity agents.
As compounds having a MCH receptor antagonistic action, the following compounds are known.
1) WO 2007/029847 (patent document 1) discloses a pyridone derivative represented by the formula:
whereinR1 and R2 are the same or different and each is a hydrogen atom, a lower alkyl group optionally having substituent(s) or a lower cycloalkyl group optionally having substituent(s), or R1 and R2 form, together with the nitrogen atom bonded thereto, an aliphatic nitrogen-containing heterocycle optionally having substituent(s),X1, X2 and X3 are the same or different and each is a methine group optionally having substituent(s) or a nitrogen atom, provided that X1, X2 and X3 are not simultaneously nitrogen atoms,Y1 is a single bond, —O—, —NR—, —S—, —SO— or —SO2—,Y2 is a lower alkylene group optionally having substituent(s), a lower alkenylene group optionally having substituent(s) or a lower cycloalkylene group optionally having substituent(s),Y3 is a single bond, —O—, —NR—, —S—, —SO— or —SO2—,each R is independently a hydrogen atom or a lower alkyl group optionally having substituent(s),W1, W2, W3 and W4 are the same or different and each is a single bond, a methylene group optionally having substituent(s) or —O—, provided that continuous two or more of W1, W2, W3 and W4 are not simultaneously —O—,L is a single bond, a methylene group optionally having substituent(s) or an ethylene group optionally having substituent(s), and L optionally forms, together with Z2, R1 and the nitrogen atom bonded to R1, an aliphatic nitrogen-containing heterocycle optionally having substituent(s),Z1 and Z2 are the same or different, and each is a single bond, a C1-4alkylene group optionally having substituent(s) or —O—,Ar1 is an aromatic carbocyclic group optionally having substituent(s) or an aromatic heterocyclic group optionally having substituent(s), andAr2 is a divalent and bicyclic aromatic carbocyclic group optionally having substituent(s) or a divalent and bicyclic aromatic heterocyclic group optionally having substituent(s), or a pharmaceutically acceptable salt thereof.2) WO 2008/086409 (patent document 2) discloses a compound represented by the formula:
whereinn is 1 or 2,R is NR1R2 wherein, R1 and R2 are each independently selected from H and optionally substituted alkyl, or R1 and R2 form, together with the adjacent N atom, a 4- to 7-membered optionally substituted heterocycle optionally containing 1 or 2 hetero atoms in addition to the N atom,R3 and R4 are each independently selected from H and alkyl, or R, R3 and R4 can form, in combination, optionally substituted imidazolin-2-yl,B is aryl or heteroaryl, andR5, R6 and R7 are each independently selected from H, —OH, —O-alkyl, alkyl, halo, —CF3 and —CN,provided the aforementioned compound is not one of the following
3) Bioorg. Med. Chem. Lett., 20(23), 7015-7019 (2010) (non-patent document 1) discloses a compound represented by the following formula:
wherein R is 2-(dimethylamino)ethyl, 2-(pyrrolidin-1-yl)ethyl, (4,5-dihydro-1H-imidazol-2-yl)methyl or the like.4) WO 2011/130086 (patent document 3) and WO 2011/127643 (patent document 4) disclose a compound represented by the formula:
whereinR1 and R2 are each independently selected from the group consisting of halogen, hydrogen, —OH, C1-C6 alkyl, —OC1-C6 alkyl, —O-halogen-substituted C1-C6 alkyl and halogen-substituted C1-C6 alkyl;W is —N— or —CH—;Q is —O—, —NH— or —C—, or forms heteroaryl together with R4, aromatic ring B and R3;R3 is halogen, hydrogen, —OC1-C6 alkyl, C1-C6 alkyl, —O-halogen substituted C1-C6 alkyl, halogen-substituted C1-C6 alkyl, cyano, SO2C1-C6 alkyl or forms a heteroaryl ring together with aromatic ring B, Q and R4;R4 is hydrogen, oxo, C1-C6 alkyl, halogen-substituted C1-C6 alkyl or forms heteroaryl together with aromatic ring B, R3 and Q, or forms C3-C6 cycloalkyl together with R5;R5, R6 and R7 are each independently selected from the group consisting of hydrogen, C1-C6 alkyl, halogen-substituted C1-C6 alkyl, C3-C6 cycloalkyl, halogen-substituted C3-C6 cycloalkyl, C1-C6 alkyl C3-C6 cycloalkyl, —OH, C1-C6 alkyl-OH and —OC1-C6 alkyl, or R5 forms oxo group or C3-C6 cycloalkyl together with R6, or R5 forms C3-C6 cycloalkyl together with R4, and at least one of R5, R6 and R7 is not hydrogen, andn is 1-3,or a pharmaceutically acceptable salt thereof.5) WO 01/82925 (patent document 5) discloses a compound represented by the formula:
whereinAr1 is a cyclic group optionally having substituent(s);X and Y are the same or different and each is a spacer wherein the main chain has 1 to 6 atoms;Ar is a fused polycyclic aromatic ring optionally having substituent(s);R1 and R2 are the same or different and each is a hydrogen atom or a hydrocarbon group optionally having substituent(s), or R1 and R2 optionally form, together with the adjacent nitrogen atom, a nitrogen-containing heterocycle optionally having substituent(s), R2 optionally form, together with the adjacent nitrogen atom and Y, a nitrogen-containing heterocycle optionally having substituent(s), and R2 optionally form, together with the adjacent nitrogen atom, Y and Ar, a nitrogen-containing fused ring optionally having substituent(s),or a salt thereof.
On the other hand, as a p38 MAP kinase modulator, the following compound is known.
6) WO 03/068230 (patent document 6) and WO 2005/018557 (patent document 7) disclose a compound represented by the formula:
whereinR1 is H, halogen or the like,R2 is optionally substituted arylalkoxy, optionally substituted heteroarylalkyl or the like,R3 is H, halogen or the like,R4 is H or optionally substituted alkyl, andR5 is aryl optionally substituted by substituent(s) such as C3-C7 cycloalkyl, alkoxyalkyl and the like, and the like or a pharmaceutically acceptable salt thereof, and Example 641 discloses a compound represented by the following formula:

As the VEGF receptor 3 inhibitor, the following compound is known.
7) WO 2008/070599 (patent document 8) discloses a compound represented by the formula:
wherein X1, X2, X3, X4, X5, X6 and X7 are each independently C or N,X8 and X9 are each independently C or N+,R1, R2, R3, R4, R5, R6 and R7 are each independently H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C20 cycloalkyl, C3-C20 cycloalkenyl, C1-C20 heterocycloalkyl, C1-C20 heterocycloalkenyl, aryl, heteroaryl, halogen, CN, NO2, ORa, COORa, OC(O)Ra, C(O)Ra, C(O)NRaRb, C(O)N(Ra)N(Rb)C(O)Rc, NRaRb, N(Rc)SO2NRaRb, SO2NRaRb, or SRa,Ra, Rb and Rc are each independently H, C1-C10 alkyl, C3-C20 cycloalkyl, C1-C20 heterocycloalkyl, aryl or heteroaryl, or Ra and Rb form, together with the nitrogen atom bonded thereto, C1-C20 heterocycloalkyl or heteroaryl and, as compound 52, a compound represented by the following formula is disclosed.
